Manufacture of indazoles

ABSTRACT

Preparation of indazoles by reacting o-toluidines with alkyl nitrites, esters of glycols or glycol derivatives with nitrous acid, and/or nitrous gases in the presence of acetic anhydride, an alkali metal salt of an alkanoic acid and an organic solvent followed by elimination of the acetyl group from the 1acetylindazole formed. The compounds prepared by the process of the invention are valuable intermediates in the manufacture of dyes, pharmaceuticals and pesticides.

baited States atent I191 Quecharrlt et a1.

[ 1 Jan. 28, 1975 I MANUFACTURE OF INDAZOLES [75] Inventors: Christoph Ruechardt, Burghoefen bei Kirchzarten; Volker Hassmann, Muenster; l-lans-Juergen Quadheclt-Seeger, Ludwigshalcn; Herbert Armbrust, Gruenstadt, all

[21] Appl. No.: 304,241

[30] Foreign Application Priority Data Nov. 9, 1971 Germany 2155545 Mar. 3, 1972 Germany 2210169 [52] US. Cl. 260/310 C, 260/141 [51] Int. Cl C07d 47/18 [58] Field of Search 260/310 C [56] References Cited UNITED STATES PATENTS 3.705.175 12/1972 Macdanyl ct a1. 260/310 C FOREIGN PATENTS OR APPLICATIONS 400,169 4/1966 Switzerland 260/310 C OTHER PUBLICATIONS Behr In: Wiley et al., Pyrazoles, IPyrazoIines, Pyrazolidines, Indazoles and Condensed Rings N.Y., Intersciencc-Wiley, 1967, page 300. Elderfield. Hcterocyclic Compounds, V01. 5, pages l7l4, N.Y., Wiley, 1957. Huisgcn ct al.. Liebigs Anna]. Chem, Vol. 586, pages 84109(I954). Simonov et al., Chem. Abst. Vol. 59, col. 10021 I963). Simonov et al., 11 Zhur. Obshch. Khim.. Vol. 33. pages 1001-5 1963. I

Primary Examiner-Natalie Trousof Attorney, Agent, or Firm-.1ohnston, Keil, Thompson & Shurtleff [57] ABSTRACT Preparation of indazoles by reacting o-toluidines with alkyl nitrites, esters of glycols or glycol derivatives with nitrous acid, and/or nitrous gases in the presence of acetic anhydride, an alkali metal salt of an alkanoic acid and an organic solvent followed by elimination of the acetyl group from the l-acetylindazole formed. The compounds prepared by the process of the invention are valuable intermediates in the manufacture of dyes, pharmaceuticals and pesticides.

12 Claims, N0 Drawings This invention relates to a process for the manufacture of indazoles by reacting o-toluidines with alkyl nitrites, esters of glycols or glycol derivatives with nitrous acid, and/or nitrous gases in the presence of acetic anhydride, an alkali metal salt of an alkanoic acid and an organic solvent followed by elimination of the acetyl group from the l-acetylindazole thus formed.

It is disclosed in Annalen der Chemie, Vol. 586 (1954), pp. 84-109, and in Eldertield, Heterocyclic Compounds, Vol. 5, pp. 162-192 (J. Wiley, New York, 1957) that substituted o-toluenediazonium salts may be cyclized to form indazoles. The yields are only high when the substituents are electron-attracting (Albert, Chemie der Heterocyclen (Verlag Chemie, Weinheim, 1962), pp. l92-l93). For example, mnitro-o-toluenediazonium compounds are cyclized in acetic acid to form 6-nitroindazole (Elderfield, loc. cit., pp. 171 and 172). It is pointed out that the substituent must be a nitro group or a halogen atom. It is also known to treat benz-o-toluidide in acetic acid with nitrous gases and precipitate the resulting nitroso compound with water and then separate it and heat it in benzene to convert it to indazole (Elderfield, loc.cit., page 172; Annalen, loc. cit., page 89). As disclosed in the said article in Annalen (loc. cit., page 85), otoluenediazonium salts, when in acidic or neutral solution, do not provide indazole but give rise to normal exchange reactions with the elimination of the diazo nitrogen. It is recommended (Annalen, loc. cit., page 90) to nitrosate acet-o-toluidide in a mixture of acetic acid and acetic anhydride, to precipitate the nitroso compound with water, to separate and dry it and then to cyclize it in benzene at 40C.

All of these processes are complicated and unsatisfactory in operation, in their economics and in their yields of product when carried out on a commercial scale. The above nitroso intermediates are unstable and difficult to isolate and to dry completely, as is necessary for the subsequent cyclizing operation.

It is an object of the present invention to provide a new process for the manufacture of indazole itself and indazoles substituted with electron-repelling substituents, in better yield and purity and in a simpler and more economical manner.

We have found that indazoles of the general formula where R and R have the meanings stated, are reacted with alkyl nitrites, esters of glycols or glycol derivatives with nitrous acid, and/or nitrous gases in the presence of acetic anhydride, an alkali metal salt of an alkanoic acid and an organic solvent which is inert under the conditions of the reaction, and the acetyl group is then removed from the resulting l-acetyl-indazole in known manner.

The reaction may be represented by the following equation illustrating the use of o-toluidine and isoamyl nitrite:

C E -ONO NH 5 9 (CH C- 0 E -C H 0H CH jq CH -C-OH H 0 9 H O c-n a' 3 CH COOH ii 3 The reaction may also be represented by the following equation illustrating the use of o-tuluidine and the nitrite of glycol monomethyl ether:

q ca oca -cn ono (CH -(F) O -CH OCH m crr -c-on H O I (3:0 H O irH CH -CH COOH g Compared with the prior art processes, the process of the invention provides indazole and indazoles substituted with electron-repelling substituents in surprisingly better yield and purity and in a simpler and more economical manner. There is no complicated and costly preparation and isolation of nitroso derivatives. The simple, single-stage method of cyclization makes the process suitable for use on a commercial scale.

The process of the invention, when using esters of glycol or glycol derivatives with nitrous acid, produces indazoles and substituted indazoles in generally shorter reaction times than when alkyl nitrites and nitrous gases are used.

Preferred starting materials of formula II and accordingly preferred products l are those in the formulae of which the radicals R, which may be the same or different. are hydrogen, alkyl of from 1 to 6 carbon atoms, cycloalkyl of 5 to 6 carbon atoms, aralkyl of from 7 to 12 carbon atoms, phenyl, chlorine, bromine or iodine and R is hydrogen or alkyl of from 1 to 6 carbon atoms. The above radicals may be substituted by groups which are inert under the conditions ofthe reaction, for example alkyl or alkoxy groups of from 1 to 3 carbon atoms. The radicals R are preferably in the 2-, 3- and/or 4-positions in relation to the amino group in starting material II.

Examples of suitable starting materials 11 are: tuluidine, 2-methyl-, 2,3-diisopropyl-, 2-ch1oro-, 3- chloro-, 4-chloro-, 5-ch1oro-, 3-phenyl-, 4-ethyl-, 2,4- dichloro-, 3-cyclohexyl-, 2bromo-, 2-iodoand 4-benzyl-o-toluidines, o-ethylaniline and o-n-butylaniline.

The reaction is carried out in the presence of acetic anhydride, preferably in an amount of from 100 to 2,300% and in particular from 280 to 860% by weight based on starting material 11, and in the presence of an alkali metal salt of an alkanoic acid, preferably in an amount of from to 360% and in particular from 90 to 190% by weight based on starting material 11. Preferred salts are the sodium and potassium salts, and suitable acids are those having from 1 to 6 carbon atoms. Specific examples of suitable salts are the sodium and potassium salts of propionic acid, butyric acid, isobutyric acid, valeric acid and capronic acid and, in particular, potassium acetate.

Suitable organic solvents which are inert under the conditions of the reaction are aromatic hydrocarbons such as the xylenes, toluene and, in particular, benzene; aliphatic hydrocarbons such as light petroleum and petroleum ethers, cycloaliphatic hydrocarbons such as cyclohexane, and appropriate mixtures thereof. In general, suitable amounts are from 800 to 25,000% and in particular from 2,000 to 3,000% by weight of solvent, based on starting material II.

Suitable further starting materials are nitrosating agents in the form of alkyl nitrites and preferably in the form of an alkyl nitrite having from 1 to 5 carbon atoms, or in the form of nitrous gases. Specific examples are methyl, ethyl, amyl, isobutyl and, in particular, isoamyl nitrites. By nitrous gases we mean the nitrogen oxides known to be useful as nitrosating agents or diazotizing agents, i.e. nitric oxide, nitrogen dioxide, nitrogen tetroxide and nitrogen trioxide. These gases may be used separately or, preferably, as a suitable mixture, advantageously a mixture of nitric oxide and nitrogen dioxide. In general, amounts of from 1.1 to 5 moles of alkyl nitrite and/or nitrous gases per mole of starting material 11 and advantageously from 1.1 to 2.7 and more particularly from 1.1 to 1.7 moles of alkyl nitrite or from 1.5 to 5 and more particularly from 2 to 4 moles of N 0; per mole of starting material 11 are suitable. Gases which are inert under the conditions of the reaction, e.g. nitrogen, may be added to said nitrogen oxides or mixtures thereof.

The esters of nitrous acid, which may be used as further starting materials, can be prepared in any desired manner, conveniently by the reaction of glycol or glycol derivatives with nitrous acid or nitrogen oxides. Preferred esters of glycols and glycol derivatives are monoand di-glycol esters of nitrous acid having the formula 111 where R is a radical of the formula -R -O or where R is an aliphatic radical and R is hydrogen or an aliphatic radical, n is one of the numbers 1, 2, 3 and 4 and X is the group NO or an aliphatic, araliphatic, cycloaliphatic or aromatic radical. Advantageously, R is alkylene of from 3 to 12 and in particular from 4 to 9 carbon atoms, R is hydrogen or alkyl of from 1 to 4 carbon atoms, in particular methyl, n is one ofthe numbers l, 2 and 3 and X is the group NO, alkyl of from 1 to 4 carbon atoms, aralkyl of from 7 to 12 carbon atoms, cyclohexyl, cyclopentyl, phenyl, or alkylcarbonyl of from 2 to 5 carbon atoms, advantageously acetyl. The said alkyl and alkylene radicals may be straightchain or branched-chain. The above preferred radicals may also be substituted by groups which are inert under the conditions of the reaction, e.g. alkoxy or alkyl each of from 1 to 3 carbon atoms. In general, suitable quantities are from 1.1 to 5 moles of monoglycol ester per mole of starting material II and conveniently from 1.1 to 2.7 and more particularly from 1.1 to 2.2 moles of monoglycol ester per mole of starting material 11. Suitable amounts of diglycol esters are accordingly from 0.55 to 2.5 and conveniently from 0.55 to 1.35 and more particularly from 0.55 to 1.1 moles per mole of starting material 11. Suitable esters III are for example monoor di-esters of nitric acid with the following compounds:

CH CH CH CH COOCH CH OH (onlinuctl (CHECHQWEH CH O (CH CH W H C2H50(CH2CH2O)3H, HECQ-OCHQCHQOH, CHBOQ-OCHQCHQOH @o(cH cH o) H,

H .3 C H5O(CH CH O) n, cllglycol esters 1n whleh R 1s R O x is l-lO and R is the alkylene radical (CH2)3, -(cn The reaction is usually carried out at a temperature of between 45 and 130C and preferably of between 60 and 110C at atmospheric or elevated pressure, continuously or batchwise. For example, the starting materials may be reacted in the following manner: a mixture of starting material ll, alkyl nitrite or ester, acetic anhydride, alkali metal salt and solvent is maintained at the reaction temperature for from 12 to 20 hours. The mixture is then filtered and the filtrate evaporated.

The product is present in the filtrate in the form of its l-acetyl compound. The acetyl group is removed in known manner, conveniently by treatment with acid in an amount of, say, from 2 to moles per mole of lacetyl compound for from 30 to 90 minutes at from 40 to 60C. In the case of chloroindazoles the temperature used in conveniently from 60 to 70C and, if necessary, slightly higher amounts of acid are used for the saponification. Advantageously, to 38% w/w hydrochloric acid is used. However, elimination of the acetyl group may be carried out with other acids, such as 48% w/wsulfuric acid, 64% w/w phosphoric acid or 33% w/w nitric acid.

After the elimination of the acetyl group, the product is isolated in conventional manner, for example by extracting the mixture with benzene, extracting the benzene extract with hydrochloric acid, supersaturating the hydorchloric acid extract with ammonia and filtermg.

If, in place of alkyl nitrite, nitrous gases are used, one of the said nitrogen oxides or mixtures thereof, usually N 0 may be passed, optionally together with inert gas, continuously or intermittently through the starting mixture at the reaction temperature over a period of from 90 minutes to 4 hours, the reaction then being carried out for from to 90 minutes followed by isolation of the product in the manner described above.

The compounds prepared by the process of the invention are valuable intermediates in the manufacture of dyes, pharmaceuticals and pesticides. For example, valuable azo dyes may be obtained by coupling (Bamberger, Annalen, 305, pp. 298, 299 and 343; Belgian Patent 623,968).

In the following Examples the parts are by weight unless otherwise stated. The parts by weight relate to the parts by volume as do kilograms to liters.

EXAMPLE 1 Isoamyl nitrite as diazotizing agent 3.51 parts of isoamyl nitrite are added to a suspension of 2.14 parts of distilled o-toluidine and 2.0 parts of anhydrous potassium acetate in 6.13 parts of acetic anhydride and '60 parts by volume of benzene over a period of 30 minutes. The reaction solution is held at from to C with constant stirring. After a reaction period of 18 hours, during which the solution takes on an orange-red color, the cooled reaction solution is filtered to remove the potassium acetate, which is washed a number of times with benzene. The combined filtrates are evaporated at 40C in a rotary evaporator, and a mixture of 10 parts by volume of 5 N hydrochloric acid and 5 parts by volume of concentrated hydrochloric acid is slowly added to eliminate the acetyl group. The mixture is then stirred at from 45 to 50C for 1 hour and heated to 55C for a short period. The reaction solution is shaken with 55 parts by volume of benzene and the benzene phase is then extracted with l X 10 parts by volume of 2N hydrochloric acid and 2 X 5 parts by volume of 5N hydrochloric acid. The acid extracts are treated with from 10 to l5 parts by volume of concentrated ammonia to separate the indazole. After standing for 2 hours in an ice bath, the product is filtered off, washed with cold water and dried in vacuo over concentrated sulfuric acid. The yield is 1.86

parts (78.5% of theory) of indazole, m.p. 147.5 to 148.0C.

If the reaction is carried out in solvents other than benzene, the yields of indazole are as given in Table 1 EXAMPLES 2 TO 8 Example 1 is repeated except that the following starting materials 11 are used:

Example Starting material 11 Parts 2 3-methyl-6-aminotoluene 2.42 3 4-methyl-6-aminotoluene 2.42 4 5-methy1-6-aminotoluene 2.42 5 2-chloro-6-aminotoluene 2.82 6 3-chloro-6-aminotoluene 2.82 7 4-chloro-6-aminotoluene 2.82 8 5-chloro-6-aminotoluene 2.82

EXAMPLE 9 Nitrous gases as nitrosating agent 2.14 parts of distilled o-toluidine are added to a suspension of 4.0 parts of anhydrous potassium acetate in 9.2 parts of acetic anhydride and parts by volume of benzene. The reaction solution is maintained at from to C over 3 hours with constant stirring. During this period, parts of nitrous gases generated from sodium nitrite and concentrated nitric acid in a closed reaction vessel are passed through the reaction solution in admixture with nitrogen as carrier gas. After a total reaction time of 4 hours the solution has assumed a red dish brown color. This reaction solution is then worked up as described in Example 1. The yield of crude indazole is 1.47 parts (62.0% of theory), its melting range being from to C. If the product is Sublimated at an oil bath temperature of 80C and a pressure of 0.05 mm of Hg, the yield is 1.13 parts of indazole (47.5% of theory) having a melting range of from 144 to 147C.

EXAMPLES 10 TO 12 The following reactions are carried out in the manner described in Example 9 and the results are given in Table 111.

TABLE [I1 Ex. Starting material Parts lndazolc Parts Yield in m.p.

product of theory C 10 2-chloro-6-amino- 2.82 4-chloro- 2.32 76.1 155.5l56

toluene indazole l1 3-chloro-6-amino- 2.82 5-chloro- 1.90 62.4 114.5-116 toluene indazole 12 4chloro-6-amino- 2.82 6-chloro- 1.76 57.5 174-l76 toluene indazole The saponification temperature in Examples 5 to 8 is from 60 to 70C and the acid used is 10 parts by volume of concentrated hydrochloric acid mixed with 5 parts by volume of 5N hydrochloric acid. The results are listed in Table 11 below.

EXAMPLES 13 TO 14 In Table IV below, the reaction given in Example 13 is carried out with isoamyl nitrite in a manner similar to that described in Example 1, and the reaction given 45 in Example 14 is carried out with nitrous gases and N TABLE IV Ex. Starting material Parts Product Parts Yield in m.p.

% of theory C 13 o-ethylaniline I 2.42 3-methyl- 1.44 54.6 109-111 indazole 14 o-ethylaniline 2.42 3-methyl- 0.88 33.4 108-110 indazole TABLE II as carrier gas in a manner similar to that described in Example 9.

EXAMPLE 15 0 indazole product Pans Yield in mp. 3.9 parts of dnsopropyldiglycol dinitrlte are added at of theory 80 to 85C to a mixture of 2.14 parts of o-toluidine, 8 2 imethylindamle L7] 648 l '44 16 parts of acetic anhydride, 2 parts of anhydrous potas- 3 3.,flflfiy1indazo1e L82 68,9 175476 slum acetate and 60 parts by volume of dry benzene. 4 7-met ylindazole 1.45 54.9 134-135 5 Mhhmindazole 253 830 155456 65 The mixture IS stirred under reflux for 30 minutes and g, gwmomindazole 246 80.8 HM then cooled and filtered. The precipitate, which sub- -c oroindazole 2.51 82.4 174-176 8 7 chloroindamle 1.66 54.5 35436 stantially consists of potassium acetate, 18 washed a number of times with benzene. The combined filtrates are evaporated in vacuo below 40C and to the residue col derivatives are reacted with o-toluidine to give the there are added 10 parts by volume of 5N hydrochloric indazole yields listed in Table VII below. acid and 5 parts by volume of concentrated hydrochlo- TABLE V ric acid, this mixture then being stirred for 45 minutes at 45 to 50C and, after the addition of a little acti- 5 Ex. Parts of Glycol moiety of ester used Yield of vated charcoal, the mixture filtered. The filtrate IS ester used indazole cooled, and w/w aqueous ammonia is added until T 3 the mixture is alkaline, after which the mixture is illtered and the product is dried to give 2.19 parts of lo 23 2.3 gietgyleneglycol (diestenh I Z;

24 .7 iet yleneg yco monomet yether crude indazole. 'lLhrs 1S purified by sublimation at 0.1 25 43 ehyleneglycol monomeuhylether 67 mm of Hg and 80 C to give 1.82 parts of indazole hav- 26 8.3 triethyleneglycol monoelhylether 57 ing a melting range of from 144 to 146C (77.2% of 27 ethyleneglym] 52 28 5.7 ethyleneglycol monopro'pylether 65 theory). 1f the reaction 18 carried out in solvents other 29 (L0 gthyleneglycol monobutylether 66 30 3.0 butanediol-l,4 (diester) 71 than benzene, the indazole yields given in Table V are 15 31 4.2 triethyleneglycol (dimer) 54 obtained.

TABLE V Solvent Temperature Reaction time Yicld in 74 m.p.

hrs of theory "C cyclohexane 80 30 70 143-144 light petroleum 8O 7 30 58 146-147 petroleum ether 45 65 g 52 143-144 EXAMPLES 16 TO 22 30 We claim: Example 15 is repeated except that the following 1. A process for the manufacture of an mdazole of starting materials are used. the formula Example Starting material Parts 2 l u 16 3-methy1-6-aminotoluene 2.42 a N 17 4-methy1-6-aminotoluene 2.42 I 18 S-methyl- 6-aminotoluene 2.42 11% H 19 2-ch1oro-6-aminotoluene 2.82 2O 3-chloro-6-aminotoluene 2.82 40 21 4-ch1oro-6-aminotoluene 2.82 22 5-chloro-6-aminotoluene 2.82

wherein The saponification temperature in Examples 19 to 22 R, and R each is hydrogen, alkyl of from 1 to 6 caris 60C to 70C and the acid used is a mixture of 10 bon atoms, benzyl, chlorine, bromine or iodine, and R parts by volume of concentrated hydrochloric acid and is hydrogen or alkyl of from 1 to 6 carbon atoms, with 5 parts by volume of 5N hydrochloric acid. The results the proviso that the R and R radicals may bear an are listed in Table VI below. inert substituent selected from the group consisting of alkyl and alkoxy each of from 1 to 3 carbon atoms, which process comprises reacting at a temperature of between 45 and 130 C. an o-toluidine of the formula TABLE VI R Ex. lndazole product Yield m m.p. in C of theory CH2 16 S-methylindazole 63 1 12-1 14 17 6-methylindazole 69 M476 2 l 18 7-methylindazo1e 57 133-135 19 4-chloroindazole 79 152-154 R% NH II 20 S-chloroindazole 73 1 15-1 16 21 t'a-chloroindazolc 78 173-174 22 7-ch1oroindazo1c 61 134-135 where R,,, R,, and R have the meanings stated, with a nitrosating agent selected from the class consisting of nitrous gases, EXAMPLES 23 TO M alkyl nitrites having from 1 to 5 carbon atoms, and Example 15 is repeated except that the following esters of glycols or glycol derivatives with nitrous monoand di-esters of nitrous acid with glycols and glyacid having the formula where R is a radical of the formula where R3-is alkylene of from 3 to 12 carbon atoms, R is hydrogen or alkyl of from 1 to 4 carbon atoms, n is one of the numbers 1, 2, 3 or 4 and X is NO, alkyl of from 1 to 4 carbon atoms, aralkyl of from 7 to 12 carbon atoms, cyclohexyl, cyclopentyl, phenyl, or alkylcarbonyl of from 2 to 5 carbon atoms, with the proviso that all of said radicals represented by R, R and X may bear an inert substituent selected from the group consisting of alk oxy and alkyl each of from 1 to 3 carbon atoms, said reaction being carried out in the presence of acetic anhydride, an alkali metal salt of an alkanoic acid having from 1 to 6 carbon atoms and an organic solvent which is inert under the conditions of the reaction.

2. A' process as claimed in claim 1, wherein the reaction is carried out in the presence of acetic anhydride in a concentration of from 100 to 2,300% by weight based on starting material 11.

3. A process as claimed in claim 1, wherein the reaction is carried out in the presence of an alkali metal salt of an alkanoic acid in a concentration of from 10 to 360% by weight based on starting material ll.

4. A process as claimed in claim 1, wherein the reaction is carried out in the presence of sodium or potassium salts of acids having from 1 to 6 carbon atoms.

5. A process as claimed in claim 1, wherein the reaction is carried out in the presence of organic solvents which are inert under the conditions of the reaction and which are present in a concentration of from 800 25,000% by weight based on starting material ll. 6. A process as claimed in claim 1, wherein the reaction is carried out using an alkyl nitrite having from 1 5 carbon atoms. 7. A process as claimed in claim 1, wherein the reac- 8. A process as claimed in claim 1, wherein the reaction is carried out using from 1.1 to 2.7 moles of alkyl nitrite per mole of starting material II.

9. A process as claimed in claim 1, wherein the reaction is carried out using from 1.5 to 5 moles of N 0 per mole of starting material I1.

10. A process as claimed in claim 1, wherein the reaction is carried out at a temperature of between 60 and C.

11. A process as claimed in claim 1, wherein the reaction is carried out using from 1.1 to 5 moles of monoglycol esters per mole of starting material II.

12. A process as claimed in claim 1, wherein the reaction is carried out using from 0.55 to 2.5 moles of di- 30 glycol esters per mole of starting material 11. 

2. A process as claimed in claim 1, wherein the reaction is carried out in the presence of acetic anhydride in a concentration of from 100 to 2,300% by weight based on starting material II.
 3. A process as claimed in claim 1, wherein the reaction is carried out in the presence of an alkali metal salt of an alkanoic acid in a concentration of from 10 to 360% by weight based on starting material II.
 4. A process as claimed in claim 1, wherein the reaction is carried out in the presence of sodium or potassium salts of acids having from 1 to 6 carbon atoms.
 5. A process as claimed in claim 1, wherein the reaction is carried out in the presence of organic solvents which are inert under the conditions of the reaction and which are present in a concentration of from 800 to 25,000% by weight based on starting material II.
 6. A process as claimed in claim 1, wherein the reaction is carried out using an alkyl nitrite having from 1 to 5 carbon atoms.
 7. A process as claimed in claim 1, wherein the reaction is carried out using from 1.1 to 5 moles of alkyl nitrite and/or nitrous gases per mole of starting material II.
 8. A process as claimed in claim 1, wherein the reaction is carried out using from 1.1 to 2.7 moles of alkyl nitrite per mole of starting material II.
 9. A process as claimed in claim 1, wherein the reaction is carried out using from 1.5 to 5 moles of N2O3 per mole of starting material II.
 10. A process as claimed in claim 1, wherein the reaction is carried out at a temperature of between 60* and 110*C.
 11. A process as claimed in claim 1, wherein the reaction is carried out using from 1.1 to 5 moles of monoglycol esters per mole of starting material II.
 12. A process as claimed in claim 1, wherein the reaction is carried out using from 0.55 to 2.5 moles of diglycol esters per mole of starting material II. 